The ultimate goal of this project is to identify natural variants of the insulin-like-growth-factor carrier protein (IGF-CP) that exhibit enhanced therapeutic potential. Such IGF-CPs may only be synthesized in specific tissues where they interact with IGFs to carry out particular functions. For example, the IGF-CP found in the wound fluid may have different properties (stability, affinity for IGF, etc.) from that found in the serum. Several tissues and cell lines which have been shown to produce IGF-CPs as well as IGFs will be the sources for the potential IGF-CP variants. In order to test the feasibility of this approach, during Phase I, cDNA libraries corresponding to several human tissues and cell lines will be obtained (or constructed) and rapidly screened for the presence of IGF-CP genes via PCR amplification. IGF-CP genes will be isolated from these libraries, characterized, and compared at the DNA sequence level. During Phase II, variant genes will be expressed and their products tested for abilities to function as IGF carrier proteins.